Introduction:

Juvenile idiopathic arthritis is an autoimmune rheumatologic disease of unknown cause. As a complex disease, it is assumed that an interaction between genetic predisposition and environmental factors determines risk. Research to identify JIA risk factors lags behind that of other childhood autoimmune disorders of similar incidence. Over the last few years, the underlying genetic predisposition has begun to emerge, mainly through candidate gene analyses. However, few studies have examined environmental risk factors for JIA in detail, but past infection is of interest, both as a possible beneficial early life immunomodulator and an adverse trigger of disease (Ellis et al. Rheumatology 49:411-25, 2010). In 2008, we established CLARITY, a JIA Biobank that is collecting biospecimens and extensive information about environment from cases presenting to the Royal Children's Hospital (RCH), Melbourne, Victoria, Australia. A control sample of healthy children attending the RCH Day Surgery Unit for specific minor surgical procedures is also been collected. Our goal is to recruit at least 1000 cases and 1000 controls, to allow adequate statistical power to detect not only main effects but also gene-environment interactions. To date we have recruited 260 cases and 400 controls.

Methods:

Here we concentrate on a preliminary analysis of a subset of the environmental measures collected in 224 incident and prevalent cases (mean age 9.5 ± 4.5 SD yrs, 69% female) and 272 controls (mean age 7.3 ± 4.1 SD yrs, 39% female) so far entered into a database. We examined the incidence of common childhood illnesses by logistic regression (adjusted for age and sex).

Results:

A history of illness such as gastroenteritis (Adjusted odds ratio (AOR) = 0.52; 95% CI: 0.32, 0.83; p = 0.006), colds and flu (AOR = 0.36; 95% CI: 0.22, 0.58; p <0.001), and chest infection (AOR = 0.44; 95% CI: 0.26, 0.74; p = 0.002) were associated with a reduced likelihood of being a JIA case. These associations remained significant when we restricted the dataset to cases diagnosed within 3 years of interview as well as cases and controls born in Victoria with four Caucasian grandparents (case n = 100, control n = 223). The associations between reduced JIA risk and childhood illness remained particularly strong and consistent for colds and flu (AOR = 0.38; 95% CI: 0.21, 0.68, p = 0.001). We then further restricted the dataset to test the association of the incidence of colds and flu prior to school entry (4 years or younger) with diagnosis of JIA at 6 years or greater (case n = 113, control n = 272). The association was observed in this subgroup (AOR = 0.42; 95% CI: 0.15, 0.82; p = 0.016).

Conclusions:

To date, these findings are consistent with other work indicating early life microbial exposure that leads to an increased incidence of common childhood illnesses confers protection against autoimmune disease, potentially through more efficient priming of the developing immune system. Further analyses will be undertaken in the larger study to examine whether the indications for control day surgery influenced these findings.